Wu, Bingchen
(2025)
Multimodal Implantable Microelectrode Arrays for Neuromodulation, Neural Recording, and Neurochemical Sensing with Stable Tissue/Device Interface.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Neural Interface technologies have seen remarkable progress, particularly with implantable microelectrode arrays (MEAs), which have become indispensable tools in neuroscience research, neurological diagnostics, and therapeutic interventions. The majority of MEAs have been developed for electrically interfacing with the neurons by recording the electrophysiological activities of neurons and/or electrically stimulating the nervous system.
However, information in the brain propagates via electrical activities and chemical signaling that involves neurotransmitters and neuromodulators, highlighting the need for MEA devices capable of both electrical and chemical interfacing. Multi-modality MEAs capable of recording neural activity (both electrical and chemical) and precisely perturbing neural circuits through neuromodulation techniques are of great value for both basic neuroscience research and clinical applications. Such capabilities are crucial for deciphering the complex interplay between electrical and chemical brain signals, which underpin high-level cognitive functions and various neurological disorders. This thesis explores the design, functionality, and application of multimodal MEAs, emphasizing the significance of their integration into neural tissue for holistic understanding and modulation of brain dynamics. On the front of neuromodulation, we developed a flexible MEA for controlled chemical stimulation and electrophysiological recording. Using conducting polymer coatings, controlled solventless drug delivery in vivo was achieved. The MEAs’ recording and neuromodulation capability was validated with acute in vivo experiments in rat models. We then introduced an antifouling zwitterionic polymer poly(sulfobetaine
v
methacrylate) (PSB) to improve device/tissue integration and functional performance. The DNA aptamer-based electrochemical cocaine sensors with PSB coating demonstrated resistance to biofouling and enzymatic degradation, maintaining high sensitivity in vivo that was previously not achieved. We also developed a dual-mode dopamine (DA) sensing and electrophysiology recording MEAs that can synchronously track tonic dopamine and neuronal dynamics stably for 4-weeks in vivo. We demonstrated the role of the Clock (a circadian master gene) in DA dynamic regulation using this technique. Lastly, utilizing PSB coatings, we optimized the technique to achieve stable DA detection and electrophysiology recording in free-moving ClockΔ19 mutant mice for 4 weeks. In summary, this thesis aims to pave the way for the development of multi-modality MEAs that hold the promise for significant breakthroughs in enhancing our understanding of the brain.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
7 January 2025 |
| Date Type: |
Publication |
| Defense Date: |
22 August 2024 |
| Approval Date: |
7 January 2025 |
| Submission Date: |
12 November 2024 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
244 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Swanson School of Engineering > Bioengineering |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Multi-modal MEA, electropphysiology, neuromodulation, neurochemical sensing |
| Date Deposited: |
07 Jan 2025 21:11 |
| Last Modified: |
07 Jan 2025 21:11 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/47075 |
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